Results In erythromelalgia case 7, we identified a novel Q10>K mutation. In CIP case 6, we identified a novel, de novo splicing mutation
(IVS8-2A>G); this splicing mutation compounded with a nonsense mutation (R523>X) and abolished SCN9A mRNA expression almost
completely compared with his unaffected father. In CIP case 5, we found a variant (P610>T) previously considered causal for
erythromelalgia, supporting recently raised doubt on its causal nature. We also found a splicing junction variant (IVS24-7delGTTT)
in all 19 patients, this splicing variant was previously considered casual for CIP, but IVS24-7delGTTT was in fact the major
allele in Caucasian populations.

Conclusions Two novel SCN9A mutations were identified, but frequently polymorphism variants are found which may provide susceptibility
factors in pain modulation. CIP and erythromelalgia are defined as genetically heterogeneous, and some SCN9A variants previously
considered causal may only be modifying factors.